This paper summarizes the experience of Professor TU Jinwen in the staged treatment of oculomotor nerve palsy （ONP） based on the theory of qi collaterals. In the acute onset stage， the key pathogenesis is triggered by wind toxin and disharmony of the qi collaterlas， for which the treatment should prioritize the elimination of pathogenic factors， with therapeutic principles of dispelling wind and eliminating toxin， boosting qi and harmonizing collaterals， using modified Qianzheng Powder （牵正散） plus Buzhong Yiqi Decoction （补中益气汤）. In the remission and recovery stage， the key pathogenesis is stagnation of blood stasis and damage to the qi collaterals， it is recommended to treat the branch， with principles of boosting qi and activating blood， resolving stasis and unblocking collaterals， using the modified Buyang Huanwu Decoction （补阳还五汤）. In the sequela and protracted stage， the key pathogenesis is depletion of the liver， spleen， and kidney with non-nourishment of the qi collaterals； the treatment should focus on addressing the root cause， with principles of fortifying the spleen and boosting qi， tonifying the liver and kidney， using the modified Sijunzi Decoction （四君子汤） combined with Qiju Dihuang Pill （杞菊地黄丸）.

OBJECTIVE To preliminarily assess the horizontal sound localization and its influencing factors in patients with unilateral sudden sensorineural hearing loss during the acute phase.METHODS The azimuth discrimination test and azimuth identification test were completed,with the speech sound(65 dB SPL)as the stimulus.The minimum audible angle(MAA)and root-mean-square error(RMSE)were obtained,and the RMSE of the affected side and the healthy side were calculated respectively.According to the WHO(2021)hearing loss classification criteria,the data were analyzed based on the pure-tone average(PTA)of the affected ear.And the best resident hearing at each frequency of the affected ear was recorded.RESULTS The performance of the unilateral sudden sensorineural hearing loss patients in the sound localization varied greatly.Some performed close to the normal level,while others completely lost the ability to localize sound.The RMSE of the moderate hearing loss group(≥35 dB HL)was significantly higher than that of the normal hearing group(P<0.01),the MAA of the moderate to severe hearing loss group(≥50 dB HL)showed statistically significant differencescompared with normal hearing group(P<0.001).The RMSE of the affected side of patients in the severe and above hearing loss group was significantly larger than that of the healthy side.Regression analysis showed that the best resident hearing at each frequency of the affected ear was the most significant factor affecting MAA(R2=0.572,P<0.001)and RMSE(R2=0.768,P<0.001).CONCLUSION The horizontal sound localization of unilateral sudden sensorineural hearing loss patients in the acute phase varies greatly.When the PTA of the affected side reaches moderate hearing loss,the localization ability is significantly lower than that of normal-hearing individuals.The best resident hearing at each frequency of the affected ear is the key factor affecting the localization ability.

Objective:To understand the incidence trend of brucellosis over time in Shandong Province from 2004 to 2023, and provide evidence for the prevention and control of brucellosis.Methods:The incidence data of brucellosis in Shandong from 2004 to 2023 were collected from China Disease Prevention and Control Information System. The annual change percentage (APC) and annual average change percentage (AAPC) of the incidence rate were calculated by using Joinpoint regression model. A age-period-cohort model was used to analyze changes in brucellosis incidence with age, period, and birth cohort.Results:The average annual incidence of brucellosis was 1.76/100 000 in Shandong from 2004 to 2023. The Joinpoint regression analysis results showed that the reported incidence of brucellosis increased by an average of 92.0% and 18.9% each year from 2004 to 2010 and from 2010 to 2014, respectively, and decreased by an average of 0.2% each year from 2014 to 2023. The results of APC model showed that the incidence of brucellosis increased first and then decreased with age ( χ2=176.92, P<0.001), and incidence of brucellosis showed slow increase and rapid increase first, then decrease ( χ2=2 921.03, P<0.001) over time. The risk for brucellosis reached peak in 2016 ( RR=5.29, 95% CI: 4.96-5.65) and became the lowest in 2006 ( RR=0.24, 95% CI: 0.21-0.28). The incidence increased in later birth cohort ( χ2=348.88, P<0.001), the AAPCs of all the age groups were between 15.0% and 40.0%, and the older the age, the greater the risk ( χ2=348.77, P<0.001). Conclusions:From 2004 to 2023, the reported incidence of brucellosis in Shandong showed a significant age-period-cohort effect, which increased first and then decreased, first increased and then decreased with age, increased slowly and rapidly first, then decreased over time, and increased in later birth cohort. It is necessary to conduct targeted prevention and control, health education to reduce the risk for brucellosis.

Objective:To investigate the correlation and causal relationship between neonatal birth weight and urinary microproteins and creatinine in adulthood.Methods:Genome-wide association studies were conducted to extract genetic loci with significant influ-ence from dataset as instrumental variables,and they were analyzed by inverse variance weighted(IVW),weighted median,MR Egger,and MR-PRESSO methods to investigate the causal relationship between neonatal birth weight and urinary microproteins and creati-nine in adulthood.A retrospective analysis was performed for 113 neonates who were admitted to Department of Neonatology,Shanxi Children's Hospital,from January 2005 to January 2007,and related data were collected during the neonatal and adult stages.A Pear-son correlation analysis was used to determine the correlation between neonatal birth weight and urinary microproteins and creatinine in adulthood.Results:The MR-IVW test showed that neonatal birth weight had a statistically significant correlation with urinary micro-proteins(P=0.037)and urinary creatinine(P=0.015)in adulthood.The retrospective study showed that there were no significant differ-ences between the two groups in all variables except body weight(P>0.05).In addition,the Pearson correlation analysis showed that neonatal birth weight was negatively correlated with urinary microproteins(r=-0.78,P=0.015)and was positively correlated with uri-nary creatinine(r=0.78,P=0.018).Conclusion:Neonatal birth weight is negatively correlated with urinary microproteins and is positively correlated with urinary creatinine in adulthood.

AIM:To investigate the effects of emo-din on autophagy and apoptosis in rats with severe pneumonia(KP)caused by K.pneumoniae and its possible mechanism.METHODS:The KP rat model was established by infecting K pneumonia was treat-ed with Emodin.The rats were grouped into Sham surgery group,KP group,low concentration Emodin group,medium concentration Emodin group,high concentration Emodin group,and Emodin+sirtinol(SIRT1 activity inhibitor)group;Arterial partial pres-sure of carbon dioxide(PaCO2),arterial partial pres-sure of oxygen(PaO2)and arterial oxygen saturation(SaO2)were measured by blood gas analyzer;the white blood cells and neutrophils in bronchoalveo-lar lavage fluid(BALF)were measured by Wright-Gi-emsa staining;HE staining was applied to detect pathological changes in lung tissue in each group;ELISA was applied to detect the expression of IL-6,TNF-α,and IL-1β in lung tissues of each group;elec-tron microscopy scanning was applied to observe the autophagy of cells in lung tissues of each group;the expression of LC3B in lung tissues was observed by immunofluorescence staining;TUNEL method was applied to detect changes in cell apoptosis in lung tissue of rats in each group;Western blot was applied to detect the expression of silent informa-tion regulatory factor(SIRT1),adenosine monophos-phate activated protein kinase(AMPK),LC3-Ⅱ,LC3-Ⅰ,c-caspase-3,and caspase-3 proteins in lung tissue.RESULTS:K.pneumoniae caused severe lung tissue damage in rats with pneumonia,increased inflam-matory infiltration and cytokine release in the lungs,arterial blood PaO2 and SaO2 levels de-creased,PaCO2 levels increased,white blood cells and neutrophils count increased in BALF,increased cell apoptosis rate and c-caspase-3/caspase-3 level,and the cell autophagy and the levels of autophagy related proteins LC3-Ⅱ/LC3-Ⅰ were decreased(all P＜0.05),after Emodin treatment,SIRT1/AMPK signal-ing pathway was activated,PaO2 and SaO2 levels in arterial blood were increased,PaCO2 levels was de-creased,inflammatory reaction was inhibited,cell apoptosis in lung tissue was inhibited(all P＜0.05),and cell autophagy level was restored,sirtinol,a SIRT1 inhibitor,partially reversed the therapeutic ef-fect of Emodin on KP rats after inhibiting SIRT1/AMPK signaling pathway(P＜0.05).CONCLUSION:Emodin may enhance autophagy of lung tissue cells and inhibit apoptosis of rat lung tissue cells by acti-vating SIRT1/AMPK pathway,which may provide po-tential therapeutic options for KP.

Objective:To understand the incidence trend of brucellosis over time in Shandong Province from 2004 to 2023, and provide evidence for the prevention and control of brucellosis.Methods:The incidence data of brucellosis in Shandong from 2004 to 2023 were collected from China Disease Prevention and Control Information System. The annual change percentage (APC) and annual average change percentage (AAPC) of the incidence rate were calculated by using Joinpoint regression model. A age-period-cohort model was used to analyze changes in brucellosis incidence with age, period, and birth cohort.Results:The average annual incidence of brucellosis was 1.76/100 000 in Shandong from 2004 to 2023. The Joinpoint regression analysis results showed that the reported incidence of brucellosis increased by an average of 92.0% and 18.9% each year from 2004 to 2010 and from 2010 to 2014, respectively, and decreased by an average of 0.2% each year from 2014 to 2023. The results of APC model showed that the incidence of brucellosis increased first and then decreased with age ( χ2=176.92, P<0.001), and incidence of brucellosis showed slow increase and rapid increase first, then decrease ( χ2=2 921.03, P<0.001) over time. The risk for brucellosis reached peak in 2016 ( RR=5.29, 95% CI: 4.96-5.65) and became the lowest in 2006 ( RR=0.24, 95% CI: 0.21-0.28). The incidence increased in later birth cohort ( χ2=348.88, P<0.001), the AAPCs of all the age groups were between 15.0% and 40.0%, and the older the age, the greater the risk ( χ2=348.77, P<0.001). Conclusions:From 2004 to 2023, the reported incidence of brucellosis in Shandong showed a significant age-period-cohort effect, which increased first and then decreased, first increased and then decreased with age, increased slowly and rapidly first, then decreased over time, and increased in later birth cohort. It is necessary to conduct targeted prevention and control, health education to reduce the risk for brucellosis.

AIM:To investigate the effects of emo-din on autophagy and apoptosis in rats with severe pneumonia(KP)caused by K.pneumoniae and its possible mechanism.METHODS:The KP rat model was established by infecting K pneumonia was treat-ed with Emodin.The rats were grouped into Sham surgery group,KP group,low concentration Emodin group,medium concentration Emodin group,high concentration Emodin group,and Emodin+sirtinol(SIRT1 activity inhibitor)group;Arterial partial pres-sure of carbon dioxide(PaCO2),arterial partial pres-sure of oxygen(PaO2)and arterial oxygen saturation(SaO2)were measured by blood gas analyzer;the white blood cells and neutrophils in bronchoalveo-lar lavage fluid(BALF)were measured by Wright-Gi-emsa staining;HE staining was applied to detect pathological changes in lung tissue in each group;ELISA was applied to detect the expression of IL-6,TNF-α,and IL-1β in lung tissues of each group;elec-tron microscopy scanning was applied to observe the autophagy of cells in lung tissues of each group;the expression of LC3B in lung tissues was observed by immunofluorescence staining;TUNEL method was applied to detect changes in cell apoptosis in lung tissue of rats in each group;Western blot was applied to detect the expression of silent informa-tion regulatory factor(SIRT1),adenosine monophos-phate activated protein kinase(AMPK),LC3-Ⅱ,LC3-Ⅰ,c-caspase-3,and caspase-3 proteins in lung tissue.RESULTS:K.pneumoniae caused severe lung tissue damage in rats with pneumonia,increased inflam-matory infiltration and cytokine release in the lungs,arterial blood PaO2 and SaO2 levels de-creased,PaCO2 levels increased,white blood cells and neutrophils count increased in BALF,increased cell apoptosis rate and c-caspase-3/caspase-3 level,and the cell autophagy and the levels of autophagy related proteins LC3-Ⅱ/LC3-Ⅰ were decreased(all P＜0.05),after Emodin treatment,SIRT1/AMPK signal-ing pathway was activated,PaO2 and SaO2 levels in arterial blood were increased,PaCO2 levels was de-creased,inflammatory reaction was inhibited,cell apoptosis in lung tissue was inhibited(all P＜0.05),and cell autophagy level was restored,sirtinol,a SIRT1 inhibitor,partially reversed the therapeutic ef-fect of Emodin on KP rats after inhibiting SIRT1/AMPK signaling pathway(P＜0.05).CONCLUSION:Emodin may enhance autophagy of lung tissue cells and inhibit apoptosis of rat lung tissue cells by acti-vating SIRT1/AMPK pathway,which may provide po-tential therapeutic options for KP.

Objective:To investigate the association between programmed cell death protein 1 (PD-1) and its ligand PD-L1 and cytokines in patients with polycystic ovary syndrome (PCOS).Methods:Using the GSE54248 dataset from the GEO database, differentially expressed PD1/PD-L1 pathway-related genes in PCOS were identified and subjected to GO and KEGG pathway enrichment analysis. In this case-control study, totally 105 patients with PCOS (named PCOS group) and 109 non-PCOS patients (named control group) who were treated at the Reproductive Assisted Reproduction Center of the First Affiliated Hospital of Xinjiang Medical University from January 2022 to June 2023 were recruited. The QBPlex flow cytometry high-throughput multiplex assay was utilized to assess the peripheral blood levels of PD-L1, PD-L2, PD-1, and cytokines in PCOS group and control group. Pearson's method was used for correlation analysis.Results:In PCOS group, the PD-1 level in peripheral blood [2.890 (0.020, 4.540) ng/L] was significantly lower than that of control group [3.370 (2.460, 4.360) ng/L, P=0.008], the PD-L1 level [9.820 (8.860, 10.880) ng/L] was lower than that in control group [10.410 (9.700, 11.160) ng/L, P=0.001]. There was no significant difference in the expression level of PD-L2 between the two groups ( P>0.05). From the GSE54248 dataset, 26 differentially expressed genes were identified, primarily enriched in the PD-1/PD-L1 pathway, Th1 and Th2 cell differentiation, and pathways associated with the production of cytokines involved in inflammatory responses. Compared with control group, PCOS group exhibited a significant decrease in the peripheral blood concentrations of interleukin (IL)-5, IL-9, IL-25, IL-10, growth stimulation expressed gene 2 (ST-2), and Granzyme B, and a significant increase in IL-8, IL-1RA, and tumor necrosis factor-α (TNF-α) levels, with all differences being statistically significant (all P<0.05). PD-1 exhibited positive correlations with the levels of IL-1RA, ST-2, and TNF-α ( r=0.270, P=0.005; r=0.213, P=0.029; r=0.291, P=0.003), while it exhibited negative correlations with the levels of IL-9, IL-25, and Granzyme B ( r=-0.322, P<0.001; r=-0.211, P=0.031; r=-0.369, P<0.001). PD-L1 demonstrated positive correlations with the levels of IL-9, IL-25, and Granzyme B ( r=0.254, P=0.009; r=0.330, P<0.001; r=0.340, P<0.001), and a negative correlation with IL-10 level ( r=-0.373, P=0.009). Conclusion:The expression of PD-1 and PD-L1 in the peripheral blood of PCOS patients is down-regulated, which may be associated with an imbalance in Th1/Th2 cytokines and serve as potential molecular biomarkers for the treatment of PCOS.

Objective:To investigate the association between programmed cell death protein 1 (PD-1) and its ligand PD-L1 and cytokines in patients with polycystic ovary syndrome (PCOS).Methods:Using the GSE54248 dataset from the GEO database, differentially expressed PD1/PD-L1 pathway-related genes in PCOS were identified and subjected to GO and KEGG pathway enrichment analysis. In this case-control study, totally 105 patients with PCOS (named PCOS group) and 109 non-PCOS patients (named control group) who were treated at the Reproductive Assisted Reproduction Center of the First Affiliated Hospital of Xinjiang Medical University from January 2022 to June 2023 were recruited. The QBPlex flow cytometry high-throughput multiplex assay was utilized to assess the peripheral blood levels of PD-L1, PD-L2, PD-1, and cytokines in PCOS group and control group. Pearson's method was used for correlation analysis.Results:In PCOS group, the PD-1 level in peripheral blood [2.890 (0.020, 4.540) ng/L] was significantly lower than that of control group [3.370 (2.460, 4.360) ng/L, P=0.008], the PD-L1 level [9.820 (8.860, 10.880) ng/L] was lower than that in control group [10.410 (9.700, 11.160) ng/L, P=0.001]. There was no significant difference in the expression level of PD-L2 between the two groups ( P>0.05). From the GSE54248 dataset, 26 differentially expressed genes were identified, primarily enriched in the PD-1/PD-L1 pathway, Th1 and Th2 cell differentiation, and pathways associated with the production of cytokines involved in inflammatory responses. Compared with control group, PCOS group exhibited a significant decrease in the peripheral blood concentrations of interleukin (IL)-5, IL-9, IL-25, IL-10, growth stimulation expressed gene 2 (ST-2), and Granzyme B, and a significant increase in IL-8, IL-1RA, and tumor necrosis factor-α (TNF-α) levels, with all differences being statistically significant (all P<0.05). PD-1 exhibited positive correlations with the levels of IL-1RA, ST-2, and TNF-α ( r=0.270, P=0.005; r=0.213, P=0.029; r=0.291, P=0.003), while it exhibited negative correlations with the levels of IL-9, IL-25, and Granzyme B ( r=-0.322, P<0.001; r=-0.211, P=0.031; r=-0.369, P<0.001). PD-L1 demonstrated positive correlations with the levels of IL-9, IL-25, and Granzyme B ( r=0.254, P=0.009; r=0.330, P<0.001; r=0.340, P<0.001), and a negative correlation with IL-10 level ( r=-0.373, P=0.009). Conclusion:The expression of PD-1 and PD-L1 in the peripheral blood of PCOS patients is down-regulated, which may be associated with an imbalance in Th1/Th2 cytokines and serve as potential molecular biomarkers for the treatment of PCOS.